Field of the Invention
The present disclosure relates to in vitro methods of evaluating xenobiotics and their effect on drug transport and metabolism.
Description of Related Art
There is an increasing number of biological drugs (“biologics”) being developed as alternative therapeutics to traditional small molecule drugs. There are significant differences between these macromolecule biologics and small molecule drugs, including the ways in which they react with the body. Cytochrome P450 (CYP) enzymes are the major enzymes involved in small molecule drug metabolism and bioactivation. Several biologics are known to suppress CYP activity and result in small molecule drug toxicity following their administration. For example, influenza and flu vaccination has been shown to suppress CYP1A2 and CYP2C9 activity and thereby impair theophylline and warfarin clearance, respectively, resulting in theophylline and warfarin toxicity. The flu vaccine is also known to impair aminopyrine metabolism after inoculation. Some bacterial endotoxins (e.g., LPS) are known to affect the oral drug clearance of antipyrine, hexobarbital, and theophylline in otherwise healthy individuals. For example, following LPS treatment, changes in antipyrine (AP) clearance were found in humans and correlated with changes in TNF and IL-6.